The aim of this investigation is to obtain the neurochemical and neuropharmacological data necessary for understanding the role of mucopolysaccharides in neural processes. There is evidence suggesting that these complex carbohydrates may be involved in the axonal transmission of the nerve impulse by affecting ion movements at the nodes of Ranvier, as well as in synaptic transmission through the binding and storage of neurotransmitter amines, or by the regulation of catecholamine biosynthesis. Other evidence indicates that mucopolysaccharides are present as an extracellular ground substance or cell surface coating in the central nervous system, where they could play an important role in the "blood-brain barrier" phenomenon. By mediating specific cell-cell interactions they may be involved in the formation of specialized types of cell contacts, such as synaptic junctions. We have previously determined the mucopolysaccharide composition of brain, studied certain aspects of mucopolysaccharide structure, and have measured the turnover of sulfate and hexosamine in the mucopolysaccharides of rat brain. In the work proposed here we plan to study the distribution and metabolism of mucopolysaccharides in neuronal, glial, and subcellular fractions of brain, and to determine whether alterations in nervous system function produced by certain selected psychotropic drugs affect the turnover of mucopolysaccharides in brain. In other studies we will investigate the macromolecular organization of brain proteoglycans, the sulfatases involved in the turnover of chondroitin sulfate and heparan sulfate, and the possible regulatory role of heparan sulfate in catecholamine biosynthesis.